US 10,894,985 B2Granted

Methods for predicting response to treatment

AssigneeSitokine Limited

InventorsLynn Doucette-Stamm, Gordon W. Duff, Kenneth S. Kornman

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Abstract

The present invention provides stratification methods and kits to identify whether an individual having an inflammation-related disorder has genotype-specific differential expression of IL-1, i.e., is a “high” or “low” producer of IL-1, such that s/he can be provided an appropriate anti-inflammatory drug and at an appropriate dose. The stratification of high or low IL-1 producers is used to guide assignment of different drug doses and therefore reduce drug toxicity and adverse events in an individual who, without stratification, may be prescribed a higher dose than needed to manage the primary indication. The use of IL-1 stratification of drug dosing would allow a better clinical benefit-risk appraisal in an individual patient.

Claims13

Dependent claims

A method of treating a human subject with elevated IL-1β, comprising steps of:

(a) selecting a human subject suspected of having, or at risk for elevated IL-1β;
(b) obtaining an isolated nucleic acid from a biological sample from the human subject;
(c) detecting the single nucleotide polymorphism (SNP) alleles in the isolated nucleic acid for each of the IL1B (−511) rs16944 C>T polymorphic locus, the IL1B (−1464) rs1143623 G>C polymorphic locus, the IL1B (−3737) rs4848306 C>T polymorphic locus, the ILIA (+4845) rs17561G>T polymorphic locus and the IL1B (+3954) rs1143634 C>T polymorphic locus;
(d) determining that the human subject has a positive IL-1 genotype pattern when the IL-1 genotype pattern obtained in (c) matches an IL-1 genotype pattern that is selected from the group consisting of:
(i) CC at rs16944, GG at rs1143623 and CT at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(ii) CT at rs16944, GC at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(iii) CC at rs16944, GG at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(iv) CT at rs16944, GG at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(v) CC at rs16944, GG at rs1143623 and TT at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(vi) CT at rs16944, GC at rs1143623, CT at rs4848306, TT or TG at rs17561 and TT or TC at rs1143634,
(vii) CT at rs16944, GG at rs1143623, CT at rs4848306, TT or TG at rs17561 and TT or TC at rs1143634,
(viii) TT at rs16944, CC at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634,
(ix) TT at rs16944, CG at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634, and
(x) TT at rs16944, GG at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634;
(e) diagnosing the human subject as having elevated IL-1β when the human subject has a positive IL-1 genotype pattern determined in step (d);
and
(f) administering a drug that inhibits IL-1β activity to the human subject diagnosed in step (e).

14 more elements

A method for determining whether a human subject would receive a therapeutic benefit from a drug that inhibits IL-1β activity comprising steps of:

(a) obtaining an isolated nucleic acid from a biological sample from the human subject;
(b) detecting the single nucleotide polymorphism (SNP) alleles in the isolated nucleic acid for each of the IL1B (−511) rs16944 C>T polymorphic locus, the IL1B (−1464) rs1143623 G>C polymorphic locus, and the IL1B (−3737) rs4848306 C>T polymorphic locus the ILIA (+4845) rs17561G>T polymorphic locus and the IL1B (+3954) rs1143634 C>T polymorphic locus;
and
(c) determining that the human subject has a positive IL-1 genotype pattern when the IL-1 genotype pattern obtained in (b) matches an IL-1 genotype pattern that is selected from the group consisting of:
(i) CC at rs16944, GG at rs1143623 and CT at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(ii) CT at rs16944, GC at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(iii) CC at rs16944, GG at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(iv) CT at rs16944, GG at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(v) CC at rs16944, GG at rs1143623 and TT at rs4848306 and any allele at the rs17561 and rs1143634 loci,
(vi) CT at rs16944, GC at rs1143623, CT at rs4848306, TT or TG at rs17561 and TT or TC at rs1143634,
(vii) CT at rs16944, GG at rs1143623, CT at rs4848306, TT or TG at rs17561 and TT or TC at rs1143634,
(viii) TT at rs16944, CC at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634,
(ix) TT at rs16944, CG at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634, and
(x) TT at rs16944, GG at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634;
(d) diagnosing the human subject as having elevated IL-1 (3 when the human subject has a positive IL-1 genotype pattern determined in step (c);
and
(e) administering a drug that inhibits IL-1β activity to the human subject diagnosed in step (d).

14 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/404,733Filed 12 Jan 2017 · us provisional application
Priority: 12 Jan 2016
Published: US 2017/0198350 A113 Jul 2017
Granted: 19 Jan 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

C12Q 1/6883
Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes: for diseases caused by alterations of genetic material
A61K 9/0048
Galenical forms characterised by the site of application: eye, e.g. artificial tears
A61K 38/16
Medicinal preparations containing peptides: peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
A61P 9/00
Drugs for disorders of the cardiovascular system